In mouse xenograft studies, when MEK inhibitor (RDEA119) was dosed orally once daily for 14 days, it caused significant inhibition and delay of tumor growth. Inhibition of pERK in tumors (the target of therapy) are observed at significantly lower concentrations compared to those required to inhibit brain. This very limited brain penetration suggests the potential for reduced central nervous system side effects, according to the company.
Defects in the RAS/RAF/MEK/ERK signaling pathway are closely associated with the development of human tumors, such as melanoma, colon, lung and thyroid cancers. RDEA119, the lead compound from Ardea’s MEK inhibitor program, is a potent, non-ATP competitive, highly-selective inhibitor of mitogen-activated ERK kinase (MEK).
Barry Quart, president and CEO of Ardea Biosciences, said: “We currently plan to initiate a Phase I study of RDEA119 in patients with advanced cancer this quarter and plan to evaluate RDEA119 for inflammatory diseases next year.”